The deregulation of glutathione metabolism is broadly identifiable in the majority of cancers as the genes involved in GSH turnover or utilization are under the transcriptional control of classical tumorigenic pathways, primarily the nuclear factor erythroid 2-related factor 2 (NRF2) signaling which drives the antioxidant response and control the transcription of glutamate-cysteine ligase, the first enzyme of the cellular GSH biosynthetic pathway. This evidence concerns the gene NFE2L2 and cancer.